This application is directed to a tablet for the buccal administration of an active ingredient. Buccal administration (in the pouch of the cheek of the subject) is particularly useful for active ingredients which show poor bioavailability upon administration through other non-parenteral modes. This poor availability can be attributed to low solubility, degradation by enzymes or destruction by acid upon passing through the intestinal tract, or first pass destruction by the liver enzymes after absorption from the gastrointestinal tract. Examples of such medicaments include: steroids such as estrogens, e.g. estradiol and derivatives such as the salt and valerate, cypionate or propionate forms; progestins, e.g. progesterone and related compounds, androgens and anabolic steroids; propranolol; thyroid hormones; analgesics such as morphine and morphine derivatives, fentanyl and sulfentanil; ergotamine derivatives (for migraine therapy); bromocriptine (for treating parkinsons disease); pH sensitive peptides and small proteins such as insulin and ACTH; physostigmine; scopolamine; verapamil; and gallopamil. It is also possible to administer compounds having good oral bioavailability buccally, but normally such medicaments would be administered orally for convenience.
Buccal administration of estradiol gives an unexpected early peak in the blood level followed by a slowly decreasing concentration. This tracks the natural occurrence of estradiol in the body, and thus is an improvement over transdermal administration, which provides a relatively constant blood level. Oral administration of estrogens such as estradiol is impractical in view of the destruction of the active ingredient in the liver shortly after absorption from the gastrointestinal tract.
Most buccal formulations are designed to provide sustained release of the active, thereby avoiding swallowing of the active ingredient due to disintegration of the dosage form. Other buccal formulations utilize a disintegrant to accelerate buccal tablet disintegration. Such disintegrants include polyvinylpyrrolidone, starch, alginic acid, formaldehyde, calcium carboxymethyl cellulose, sodium starch glycolate, and sodium carboxymethyl cellulose as disclosed in Kornblum and Stoopak, J. Pharm. Sciences 62: 43-49 (1973); U.S. Pat. No. 1,380,171; Khan and Rooke, Mfg. Chemist & Aerosol News (January 1976); and Khan and Rooke, J. Pharm. Pharmac. 28: 633-636 (1976).
Applicant has discovered a fast buccal formulation which rapidly delivers the active ingredient through the buccal route in an unexpected manner. Such a rapid delivery from a buccal formulation is useful for delivering a bolus dose to achieve a rapid rise in blood levels. Moreover, the rapid delivery of the drug from the buccal tablets unexpectedly obviates the need for an adhesive, which is required in other buccal tablets to prevent the patient from swallowing the dosage form. Such adhesive containing buccals are disclosed, for example, in U.S. Pat. Nos. 4,755,386, 4,059,686, 4,292,299, and 4,226,848.